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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Kienesberger, S; Cosic, A; Kitsera, M; Raffl, S; Hiesinger, M; Leitner, E; Halwachs, B; Gorkiewicz, G; Glabonjat, RA; Raber, G; Lembacher-Fadum, C; Breinbauer, R; Schild, S; Zechner, EL.
Enterotoxin tilimycin from gut-resident Klebsiella promotes mutational evolution and antibiotic resistance in mice.
Nat Microbiol. 2022; 7(11):1834-1848 Doi: 10.1038/s41564-022-01260-3 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Kienesberger-Feist Sabine
Co-Autor*innen der Med Uni Graz
Gorkiewicz Gregor
Halwachs-Wenzl Bettina
Leitner-Meyer Eva

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Klebsiella spp. that secrete the DNA-alkylating enterotoxin tilimycin colonize the human intestinal tract. Numbers of toxigenic bacteria increase during antibiotic use, and the resulting accumulation of tilimycin in the intestinal lumen damages the epithelium via genetic instability and apoptosis. Here we examine the impact of this genotoxin on the gut ecosystem. 16S rRNA sequencing of faecal samples from mice colonized with Klebsiella oxytoca strains and mechanistic analyses show that tilimycin is a pro-mutagenic antibiotic affecting multiple phyla. Transient synthesis of tilimycin in the murine gut antagonized niche competitors, reduced microbial richness and altered taxonomic composition of the microbiota both during and following exposure. Moreover, tilimycin secretion increased rates of mutagenesis in co-resident opportunistic pathogens such as Klebsiella pneumoniae and Escherichia coli, as shown by de novo acquisition of antibiotic resistance. We conclude that tilimycin is a bacterial mutagen, and flares of genotoxic Klebsiella have the potential to drive the emergence of resistance, destabilize the gut microbiota and shape its evolutionary trajectory.
Find related publications in this database (using NLM MeSH Indexing)
Mice - administration & dosage
Humans - administration & dosage
Animals - administration & dosage
Klebsiella - genetics
Enterotoxins - administration & dosage
RNA, Ribosomal, 16S - genetics
Ecosystem - administration & dosage
Drug Resistance, Microbial - administration & dosage
Anti-Bacterial Agents - pharmacology
Escherichia coli - genetics

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